Despite the urgent need for and the extensive efforts in developing strategies to prevent C. trachomatis urogenital tract infection, no effective vaccine is available. This may be mainly due to lack of knowledge on antigenicity and immunogenicity of all proteins encoded by chlamydial genome. Previous vaccine studies were often focused on a few selected antigens such as the major outer membrane protein (MOMP) and many of these analyses were based on denatured proteins or peptides. The available chlamydial genome sequences have made it possible to obtain a comprehensive analysis of antigenicity and immunogenicity of all chlamydial proteins in conformation-dependent assays. The C. trachomatis genome encodes approximately 300 hypothetical ORFs, many of which are both highly conserved among and unique to chlamydiae. To search for novel vaccine candidates, we have cloned approximately 400 ORFs that represent approximately 50% of the chlamydial genome, including ORFs coding for all hypothetical proteins and others that may possess the potential as vaccine candidates or have been extensively studied as vaccine candidates or pathogenic determinants. We are proposing to use microplates arrayed with each of the 400 chlamydial soluble proteins to systematically analyze both antibody and T cell responses to chlamydial infection in STD patients, which should allow us to identify novel immunodominant antigens. These novel antigens will be further evaluated for their ability to induce protective immunity against chlamydial urogenital infection in animal models. Our goal is to acquire sufficient information for developing effective chlamydial vaccines in humans.